 Research Write-Up 

http://textbookofbacteriology.net/themicrobialworld/C.tetani1.gif
Disease and Drug of Interest: 
My disease of interest is Tetanus, an infection of the nervous system caused by the bacteria 
Clostridium tetani (C. tetani). Tetanus is prevented by the administration of the DTaP vaccine in 
several intervals between infancy and age seven and then Tdap/Td boosters every ten years. 
The DTap and Tdap/Td vaccines were formed as a way to prevent tetanus, diphtheria and 
pertussis simultaneously. The vaccine is created with tetanus toxoids, which are weakened 
bacterial toxins. 


 

 

 

 

 

 


 

Figure 1- The picture above shows the structure of C. tetani. From Textbook of Bacteriologys 
website 

Motivation and Background: 
Tetanus is generally an issue of concern among people who work in agricultural situations, 
especially ones dealing with soil and animal waste. Another more common cause is contact 
with rusty nails. People with inadequate vaccination, which ranges from elderly populations in 
wealthier countries to a vast majority of citizens in underdeveloped countries, are also at a risk 
for contracting the bacteria. Early records from the BC era show that tetanus affected people 
back then as well. It was truly recognized in 1884 by Antonie Carl and Giorgio Rattone, whom 
induced tetanus in animals from an injection containing pus from a human tetanus victim. 
Around that same time period, Arthur Nicolaier induced tetanus in animals by injecting them 
with soil samples. Contact with C. tetani is primarily characterized by muscle stiffness. Many 
cases of tetanus start from lockjaw, which is when the muscles in the jaw become stiff. Other 


http://www.nature.com/neuro/journal/v5/n9/images/nn0902-823-F1.jpg
symptoms include difficulty swallowing, spasms, high blood pressure and rapid heart rate. In 
more advanced cases, pulmonary embolisms, aspiration pneumonia and death can also occur. 

Target Information: 
C. tetani primarily attacks neurotransmitters by creating a toxin named tetanospasmin which 
binds to the nerves surrounding the bacterias entryway into the body, usually a wound on the 
skin. Tetanospasmin also spreads to the spinal cord and binds to the nerve endings of the spinal 
cord. This toxin prevents the release of neurotransmitters, chemicals which send messages 
from nerves to either muscles or other nerves. The lack of these neurotransmitters distresses 
the muscles and cause spasms. 
Studies have shown that tetanospasmin causes the degradation of synaptobrevin, an integral 
membrane protein of synaptic vesicles. The degradation process is called proteolysis. 
The size of synaptobrevin is 18 kilodaltons and it has two isoforms, synaptobrevin 1 and 
synaptobrevin 2. It is found in both the central and peripheral nervous systems and endocrine 
cells. It is located on nerve endings and small vesicles in the cells. Synaptobrevin is always 
expressed in the cells and nerve endings. 
Synaptobrevin is part of the group of proteins called SNARE proteins. SNARE stands for soluble 
N-ethylmaleimide-sensitive factor activating protein receptor and helps with exocytosis of 
cellular transport vesicles. Exocytosis is when the cell pushes 
the material from vesicles out of the membrane. 

 

 

 

 

 

 

 Figure 2- The figure above shows how synaptobrevin aids in exocytosis. From Nature 
Neuroscience article 

Drug Information: 
The name of the drug in the tetanus vaccine is Adacel. Vaccination for tetanus began in the 
1940s when the toxoid for tetanus was added to the existing vaccine for diphtheria and 
pertussis. This vaccine (DTP) was used in the US until the early 1990s when adverse reactions 
were observed in patients. The FDA then created DTaP, which contains acellular pertussis, a 


type of pertussis that has antigens but no whole cells, instead of whole-cell pertussis. 
The vaccine contains trace amounts of the tetanus toxin and bacteria. However, the toxin is 
detoxified and the bacteria are not alive. When injected in the bloodstream, the immune 
system classifies both the toxin and bacteria as antigens or foreign substances. This causes the 
body, specifically white blood cells, to create proteins called antibodies in response to the 
tetanus. These antibodies stay in the body as a defense in case the body comes in contact with 
the toxins. 
Since the drug is designed to build the bodys immunity to the tetanus toxoid, the drug 
increases the effect of the targets (the neurotransmitters and synaptobrevin) by allowing them 
to function without inhibition and is therefore quite effective in preventing the symptoms of 
tetanus. Adacel does not have a schematic figure, formula, molecular weight or CAS number 
since it is not a chemical but rather a collection of three weakened diseases. Adacel does 
contain aluminum phosphate along with the samples of tetanus, diphtheria and pertussis 
because aluminum phosphate works well in going through the bodys muscles to administer the 
drug. Adacels drug number is 02240255 and is made by Sanofi Pasteur. Though Adacel is not 
patented, it was licensed for use in 2005. 
Adacel is typically administered as an injection in the arm or leg. The side effects of Adacel 
include fever/chills, tenderness or swelling at the injection site, headaches, joint pains and 
nausea. The more extreme and more uncommon side effects are fainting, high fevers and 
seizures that can result in convulsions. 
There are several controversies surrounding the administration of DTaP in young children. 
Babies generally receive their first dose of DTaP between 15-18 months and then every two 
years after that. Though there are no concrete studies to prove this, there are many people 
who believe the use of DTaP along with other preventative vaccines are the cause of autism 
and other developmental disorders in children. 
There have been at least eight clinical trials conducted in the last seven years which related to 
Adacel, but only three of them are still ongoing. There are several steps needed to create 
Adacel. First, the acellular pertussis portion is taken from Bordetella pertussis, the bacteria 
which cause pertussis. Because it is acellular, the samples taken do not contain whole cells, but 
rather a mixture of cell parts and antigens, which is done by filteration. Corynebacterium 
diphtheria, the bacteria which causes diphtheria and C. tetani are both purified by fractionation 
and diafiltered. The major alternative to Adacel is Boostrix- the only difference between the 
two is that Boostrix has no preservatives. This drug really cannot be used to treat anything but 
tetanus, pertussis and diphtheria because it is created with the bacteria which cause those 
diseases and its true function is accustoming the body to them to build immunity. 

 


Bibliography 

Adacel (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed) 
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"Adacel - Uses, Side Effects, Interactions - Drug Factsheets." C-Health. MediResource. Web. 04 
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Baumert, M.; Maycox, P. R.; Navone, F.; De Camilli, P.; Jahn, R., Synaptobrevin: an integral 
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(CDC), C. f. D. C. a. P., Notes from the field : use of tetanus, diphtheria, and pertussis vaccine 
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CDC. "Tetanus." CDC Pinkbook. Web. 4 Feb. 2012. 


"Diphtheria, Tetanus, Pertussis (DTaP) Vaccine and Immunization Information." National 
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Duman, Joseph G., and John G. Forte. "What Is the Role of SNARE Proteins in Membrane 
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Jia-Yi Li, L. E., 2 Reinhard Jahn, and Annica Dahlstriiml, 
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